Sotos syndrome

The Sotos syndrome is a rare genetic disease. It is characterized by accelerated body growth and somewhat delayed motor and language development in childhood. In adulthood, the typical symptoms are hardly noticeable.

What is Sotos Syndrome?

In the majority of cases, the cause of Sotos syndrome is a point mutation in the NSD1 gene on chromosome 5. About 10 percent of the cases are due to a deletion in this gene.
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The Sotos syndrome represents a sporadically occurring, rare malformation syndrome. It already starts prenatally to an accelerated growth with a disproportionate skull circumference (macrocephalus) and an advanced (accelerated) bone age. Motor, cognitive and language development is slowed down. In adulthood, normal intelligence often develops and typical physical symptoms become normal.

Sotos syndrome was first discovered in 1964 by the American endocrinologist Dr. Juan F. Sotos described. He determined the typical symptoms of the disease using the example of five children. More than 200 cases have now been described. The disease is very rare. Their frequency is around 1 in 14,000 newborns. There is no familial accumulation. The disease occurs sporadically, mostly a new mutation. Sotos syndrome is also called cerebral gigantism designated.

causes

In the majority of cases, the cause of Sotos syndrome is a point mutation in the NSD1 gene on chromosome 5. About 10 percent of the cases are due to a deletion in this gene. The disease is inherited as an autosomal dominant trait. Usually it occurs as a new mutation (de novo). The corresponding gene encodes a histone methyltransferase, which is involved in the regulation of transcription.

The offspring of those affected can inherit 50 percent of the disease according to the autosomal dominant inheritance. The risk of recurrence of Sotos syndrome in healthy parents is less than one percent.

Symptoms, ailments & signs

Sotos syndrome is characterized by excessive growth in childhood. Accelerated growth is already observed prenatally, so that labor often has to be initiated prematurely. Bone growth is also accelerated. The biological bone age is higher than the chronological age. The face takes on a characteristic shape.

is long and narrow with a broad and arched forehead and a high hairline and a pointed chin. A skull anomaly develops with increased distance between the eyes and a widened bridge of the nose (hypertelorism). The palate is high and pointed, and teeth erupt early. The body length is excessive with a large head circumference.

These symptoms are very typical and suggest the diagnosis of Sotos syndrome at an early stage. However, there are also non-constant symptoms that vary in degree in each person affected. Heart defects, scoliosis, malformations of the urogenital tract, increased tendon reflexes or seizures can occur. The risk of various tumors is often increased. Motor and cognitive development is delayed to varying degrees from patient to patient.

Developmental delays often occur in fine and gross motor skills. There are problems with coordination of movement and concentration. Learning to speak is also delayed, with greater understanding of the language. However, all development steps can be achieved despite the slowed development. Children with Sotos syndrome have very different intelligence quotients. Intellectual disability is not typical for the disease, but it can occur.

The behavior of the children is also often not noticeable. In individual cases, however, tantrums and aggressive behavior, sleep problems, poor social contact and compulsive behavior have been reported. The extent to which these personality disorders are related to Sotos syndrome is not clear. It is also conceivable that it is the result of any exclusion.

Perhaps some caregivers also overestimate the children's independence due to the accelerated body growth. This can create the risk of being overwhelmed and lead to aggressive behavior on the part of the children. However, some difficulties can also arise in the development of children. Convulsions, febrile seizures, neonatal jaundice, suckling difficulties with drinking and breathing problems and frequent infections of the upper respiratory tract often occur in newborns. Due to the advanced bone age in Sotos syndrome, puberty is also premature.

Diagnosis & course of disease

Even the characteristic symptoms of accelerated body growth let the doctor quickly make the suspected diagnosis of Sotos syndrome. The differential diagnoses for Sotos syndrome such as Weaver syndrome, Beckwith-Wiedemann syndrome, Fragile X syndrome, Simpson-Golabi-Behmel syndrome, or Deletion-22qter syndrome should be excluded. Furthermore, the NSD1 gene can be examined for a gene mutation.

Complications

Because of Sotos syndrome, the affected children suffer from significantly delayed development. This complaint can also have a very negative effect on adulthood, so that symptoms can also arise in old age. As a rule, the patients are also dependent on constant help from parents or relatives.

They suffer from heart defects and often from seizures. A mental handicap also occurs, so that those affected have problems with coordination and thinking. Tantrums or general aggressive behavior also occur. The affected children also suffer from sleep problems and are very often irritated as a result.

Because of the breathing difficulties, many activities or sporting activities are not easily possible for those affected, so that there are significant restrictions in everyday life. The airways are often affected by infections and inflammation. The treatment of Sotos syndrome is purely symptomatic and is usually not associated with complications.

However, this syndrome leads to a reduced life expectancy for the patient. Many everyday complaints can be alleviated thanks to various measures that should be carried out especially in early childhood.

When should you go to the doctor?

Medical treatment by a doctor is always necessary for Sotos syndrome. This cannot lead to independent healing, so that the patient is always dependent on treatment by the doctor. Only through early detection of the syndrome can further complications be prevented. Since it is a genetic disease, it cannot be treated completely or causally. A doctor should be consulted in Sotos syndrome if the person concerned suffers from significantly accelerated growth. The individual body parts are also excessively large, which can usually be seen directly with the eye.

Furthermore, heart problems or severe cramps often point to Sotos syndrome. Tumors or severe intellectual disabilities can also point to Sotos syndrome and should always be examined by a doctor. It is not uncommon for those affected to show aggressive behavior or other mental disorders.

A general practitioner or pediatrician can usually be seen at the first signs of Sotos syndrome. Further treatment depends on the exact complaints and is carried out by a specialist.

Therapy & Treatment

A causal treatment of Sotos syndrome is not possible. It is important to treat patients in a multidisciplinary manner right from the start. However, only symptomatic therapies can be carried out. Even in infancy, depending on the complications, phototherapy for jaundice, treatment of drinking difficulties and monitoring of blood sugar levels with regard to possible hypoglycaemia are necessary.

General pediatric check-ups are designed to identify complications such as scoliosis or febrile seizures so that therapies can be initiated as quickly as possible. Because of the developmental delays, early support measures should be taken with the help of occupational therapy, speech therapy, early intervention or music therapy. All support measures are to be planned depending on the child's level of development.

The prognosis for the disease is good. In adulthood, Sotos syndrome usually reaches a normal level of development with appropriate support. The physical symptoms are also normal.

prevention

It is not possible to prevent Sotos syndrome. It is a genetic disease that usually occurs sporadically. However, since Sotos syndrome is inherited in an autosomal dominant manner, the children of one parent with the disease can be affected by 50 percent.

Aftercare

As a rule, those affected with Sotos syndrome have very few or no special and direct measures and options for follow-up care available, so that the person affected should ideally consult a doctor very early to avoid the occurrence of other complaints and complications to prevent. Neither can there be a complete cure, as it is a hereditary disease.

For this reason, if the person concerned wants to have children, he should definitely have a genetic examination and advice carried out so that the Sotos syndrome cannot recur in the descendants. Since no independent healing can occur, the person affected should consult a doctor at the first symptoms and signs of the disease.

Those affected are dependent on various therapies that can limit the symptoms. Sometimes family help and care is very important and useful and can help prevent depression and other physical complaints from developing. As a rule, contact with other sufferers of Sotos syndrome is also very useful, as this often leads to an exchange of information.

You can do that yourself

Patients with a diagnosed Sotos syndrome should be advised that some complaints will normally be regulated again with advancing age.

In particular, accelerated growth does not normally represent any further impairments in adolescence or, at the latest, in adult life. Therefore, children must be fully informed about the symptoms of the disease. In addition, people from the close social environment should also be informed about the health disorder and its further development. This approach prevents unpleasant situations and can be very helpful for the child in coping with the disease in everyday life.

Since there are problems with movement processes, it is advisable that parents train their child's motor skills on a daily basis. Although physiotherapeutic measures are provided in the treatment plan, targeted training should also be carried out independently in everyday life. This improves mobility and supports well-being.

When dealing with the patient, calmness and self-confidence are particularly important. The behavioral problems can be very stressful for all those affected. Above all, regular breaks help the legal guardians to cope better with the adversities. Since a large number of those affected depend on support from their social environment for their entire life, social stability should be built up early on.